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Biomedical subjects

M Billie

Publications and source records attributed to M Billie.

12 recordsLinked to original sources

Combined effects of caffeine and alcohol on hemodynamics and coronary artery blood flow in dogs.

Alcohol intake is often followed by coffee drinking because of the universal acceptance of its sobering effect. Such effects were found inconsistent on motor functions. However, it is common belief that caffeine will antagonize the intoxicating effects of alcohol. The independent actions of caffeine and alcohol are well documented, but combined effects of short-term administration are unknown. This experimental work was designed to study the effects due to short-term administration of caffeine and alcohol on the cardiovascular system. In phase I, 30 experiments were performed in our laboratories to study the dose-response curves of both the drugs. In phases II and III, 15 dogs were subjected to 30 experiments. In phase II, caffeine, 5 mg/kg, was given i.v., followed by ethanol, 400 mg/kg i.v., and in phase III, sequence of drug administration was reversed to study the effects on hemodynamics and coronary artery blood flow. Caffeine did not show significant changes in all the cardiovascular parameters, and ethanol administration caused nonsignificant increase in heart rate, mean arterial pressure, left ventricular systolic pressure, and left ventricular (LV) mechanical work and decrease in the maximal rate of first derivative of LV pressure, stroke volume, and systemic vascular resistance. Left ventricular end-diastolic, pulmonary artery mean and right atrial pressures, pulmonary vascular resistance, myocardial oxygen consumption, and as coronary flow reserve increased as compared with controls. Combined caffeine and alcohol had synergistic effects, but when the order of drug administration was reversed (i.e., alcohol was followed by caffeine), the effect was antagonistic.

Animals

Left atrial abnormality by electrocardiogram predicts left ventricular hypertrophy by echocardiography in the presence of right bundle-branch block.

BACKGROUND: Left ventricular hypertrophy (LVH) on the electrocardiogram (ECG) may be masked in the presence of complete right bundle-branch block (RBBB). Left bundle-branch block on the ECG is associated with LVH at autopsy in 93% of hearts studied. However, RBBB does not predict LVH and the usual ECG criteria applied for LVH may not be reliable in the presence of RBBB. HYPOTHESIS: The study was undertaken to evaluate left atrial (LA) abnormality as a criterion for the diagnosis of LVH in the presence of RBBB. METHODS: Left atrial abnormality in the ECG was assessed by two independent observers as a criterion of LVH in the presence of RBBB in 100 patients, and data were compared with those of 50 patients without LA abnormality. RESULTS: Left ventricular hypertrophy was confirmed by echocardiographic determination of left ventricular (LV) mass in both groups. Observers reliably differentiated between hypertrophied and normal-sized LV in the presence of RBBB by using LA abnormality as an ECG criterion when correlated with LV mass determined by echocardiography. Observer 1 correctly detected LVH in 88% and Observer 2 in 82% of patients. False positive diagnosis was made in 12 and 18% of patients by Observers 1 and 2, respectively. Observers' performance of recognition of LA abnormality in the present study was 94%. Results showed sensitivity of 76 and 70% and specificity of 84 and 92% for Observers 1 and 2, respectively. Left ventricular mass increased significantly and was diagnostic of LVH in 92% of patients with LA abnormality. Left ventricular mass was high in 84% of patients when corrected by body surface area. LVH in the presence of RBBB by the ECG was found in only seven patients (5%) when six commonly used conventional criteria of diagnosis of LVH by ECG were employed. Regression analysis found LA abnormality to be a strong independent predictor of increased LV mass. Multiple regression analysis revealed that age, body mass index, body surface area, and frontal axis are also significant predictors of LV mass. CONCLUSION: The results obtained by the correlation of LA abnormality by ECG and LVH by echocardiography conclude that LA abnormality by ECG was significantly diagnostic of LV hypertrophy in the presence of RBBB.

Adolescent

Combined effects of alcohol and nicotine on cardiovascular performance in a canine model.

Alcohol and tobacco consumption are correlated. Smokers consume more alcohol than do nonsmokers, and alcohol consumers smoke more than do teetotalers. The independent effects of alcohol and nicotine on the cardiovascular system are well documented, but combined effects of short-term administration are unknown. This experimental work was designed to study the effects due to short-term administration of alcohol and nicotine on cardiovascular system. In phase I, 30 experiments were performed to study the dose-response curve of both the drugs. In phases II and III, 15 dogs were subjected to 30 experiments. In phase II, ethanol, 400 mg/kg, was given i.v., followed by nicotine 50 microg/kg, i.v., and in phase III, sequence of drug administration was reversed to study the effects on hemodynamics and coronary artery blood flow. The dose-response curve established the i.v. dose of ethanol, 400 mg/kg, and nicotine, 50 microg/kg. Ethanol administration caused a nonsignificant increase in heart rate (HR), mean arterial pressure (MAP), left ventricular systolic pressure (LVS), and left ventricular mechanical work (LVMW), and a decrease in maximal rate of increase of LV pressure per second (dP/dt), stroke volume (SV), and systemic vascular resistance (SVR). Left ventricular end-diastolic pressure (LVEDP), pulmonary artery mean pressure (PAM), right atrial pressure (RAP), pulmonary vascular resistance (PVR), myocardial oxygen consumption (MVO2), and average peak velocity of coronary blood flow (APV) had mild significant increases as compared with controls. Nicotine significantly increased heart rate, mean arterial pressures, LVEDP, and pulmonary artery, pulmonary capillary wedge, and right atrial pressures. Nicotine increased dP/dt (2,062-3,188; p < 0.006) and decreased APV (9 to 8; p < 0.03). Combined ethanol followed by nicotine had synergistic increase in HR, SD, MAP, LVS, LVEDP, pulmonary pressures, CO, SV, dP/dt (2,184 > 5,206; p < 0.005), MVO2, and LVMW. However, the excitatory effects of nicotine were attenuated when ethanol was administered after nicotine (dP/dt, reduced from 2,058 to 1,653; p < 0.04, and APV increased from 10 to 12; p < 0.02). We conclude that ethanol increased APV but had nonsignificant effects on the hemodynamics, whereas nicotine reduced the APV and had significant excitatory responses. In combination (i.v.), ethanol + nicotine produced significant synergistic excitatory effects. On the other hand, the nicotine + ethanol combination increased APV and caused attenuation of the excitatory effects of nicotine in dogs.

Animals

Resolution of experimental pneumothorax in rabbits by graded oxygen therapy.

BACKGROUND: Small pneumothoraces have been treated by observation and tube thoracostomy in asymptomatic patients. Using a rabbit model, we demonstrated previously that inspired oxygen at 60% FiO2 hastened the time to resolution of complete pneumothoraces compared with room air. The present study was designed to evaluate the use of lower levels of inspired oxygen and to establish a dose-response curve for the treatment of experimental pneumothoraces. METHODS: Forty New Zealand White rabbits were divided randomly into four groups: room air (21%) and 30, 40, and 50% FiO2. Experimental pneumothoraces were created in the rabbits, and the animals were placed in cages with the designated level of inspired oxygen. Serial chest radiographs were performed until the pneumothoraces resolved. RESULTS: Pneumothoraces treated with room air resolved in 61.65 +/- 12.30 hours. Those treated with 30% FiO2 resolved in 42.90 +/- 5.97 hours, with 40% FiO2 in 35.80 +/- 4.26 hours, and with 50% FiO2 in 33.80 +/- 4.66 hours. CONCLUSION: These results show a statistically significant (p < 0.01) dose-dependent improvement in the resolution of pneumothoraces with increasing levels of inspired oxygen. Supplemental oxygen therapy may be used to facilitate the resolution of small, uncomplicated pneumothoraces.

Animals

Left atrial abnormality in acute myocardial infarction.

This study assessed left atrial abnormality by electrocardiogram as a predictor of left ventricular dysfunction during acute myocardial infarction. Hemodynamic, angiocardiographic, echocardiographic, and serial creatine kinase-MB studies revealed the electrocardiogram to be a significant predictor of location of acute myocardial infarction, prevalence of occlusive disease in coronary vessels, myocardial contractility, low ejection fraction, increased left ventricular end-diastolic pressure, and serial creatine kinase-MB.

Adult

Inhalation of toluene diisocyanate is associated with increased production of nitric oxide by rat bronchoalveolar lavage cells.

Isocyanates are used commercially, particularly in the manufacture of polyurethane coatings and foam. These compounds can pose an occupational health hazard since there is a risk of respiratory disease following isocyanate exposure. The purpose of the present study was to investigate whether a single, sublethal isocyanate inhalation is associated with increased production of the free radical nitric oxide (NO). Mature male Sprague-Dawley rats were exposed to air or toluene diisocyanate (TDI; 2 ppm) for 4 hr. Indices of pulmonary function were assessed before and after exposure to TDI fumes. At 20 hr postexposure, bronchoalveolar lavage cells (BALC) and fluid were harvested. NO synthase (NOS)-dependent reactive species production by alveolar macrophages was assessed by determining N(omega)-nitro-L-arginine methyl ester-inhibitable chemiluminescence following stimulation with unopsonized zymosan. Northern blot analysis was used to index inducible NOS mRNA levels in BALC, while nitrite and nitrate (NOx) levels were measured to determine NOx levels in the lavage fluid and the production of NO by cultured adherent BALC was indexed by measuring nitrite levels. Exposure to aerosolized TDI was associated with an increase in the number of alveolar macrophages, lymphocytes, and polymorphonuclear leukocytes harvested by bronchoalveolar lavage, relative to that from air-exposed rats. NOx levels in the lavage fluid and NOS-dependent production of reactive species by alveolar macrophages were increased following TDI exposure. In addition, inducible NO production by BALC (i.e., mRNA levels and nitrite levels in BALC conditioned media) was elevated following TDI treatment. These findings indicate that pulmonary inflammatory responses induced by TDI exposure are associated with increases in inducible NO production. Therefore, the potential role of NO in the initial pulmonary response to TDI exposure warrants further investigation.

Administration, Inhalation

Combined effects of caffeine and nicotine on cardiovascular hemodynamics in canine model.

The independent effects of caffeine and nicotine on cardiodynamics are well documented, but combined effects of both are not reported. Initially, in phase I, 18 experiments were performed to study the dose-response curve of both the drugs. In phases II and III, 13 mongrel dogs were subjected to 30 experiments. In phase II, caffeine, 5 mg/kg, was given i.v. followed by nicotine, 50 micrograms/kg, and in phase III, the sequence of drug administration was reversed to study the effects on hemodynamics. In phase II, caffeine did not show significant changes in all the cardiovascular parameters, but nicotine administration after caffeine produced marked significant synergistic excitatory effects: the rate of increase of the first derivative of left ventricular pressure (dP/dt) increased from 1,101 +/- 111 to 3,194 +/- 872 (p < 0.003). In phase III, nicotine significantly increased heart rate, mean arterial pressures; left ventricular end-diastolic pressure (LVEDP); and pulmonary artery, pulmonary capillary wedge, and right atrial pressures. Nicotine increased dP/dt (964 +/- 182 to 1,639 +/- 60 mm Hg/s; p < 0.004). The excitatory effects of nicotine were attenuated by administration of caffeine (dP/dt, 918 +/- 140 reduced to 715 +/- 144 mm Hg/s; p < 0.04). Caffeine and nicotine, alone, caused nonsignificant and significant increases in hemodynamics, respectively. In combination, caffeine + nicotine administration produced significant synergistic excitatory effects in dogs. On the other hand, the nicotine + caffeine combination caused attenuation by caffeine of the excitatory effects produced by nicotine.

Animals

Caffeine and cardiac arrhythmias. An experimental study in dogs with review of literature.

In spite of widespread belief among clinicians that caffeinated drinks are linked with palpitations, tachycardia and dysrhythmia there is paucity of documentary evidence. We investigated the arrhythmogenic activity of caffeine in canine model. The alkaloid was given i.v. to perform 51 experiments in 13 anesthetized dogs in three different doses. The Low dose generated significant Sinus (S) bradycardia (70%; p < 0.006, S. arrhythmia (70%; p < 0.02), S. arrest (50%; p < 0.04), Atrial (A) ectopics (40%; p < 0.016), Wandering of pacemaker (WPM) (50%; p < 0.04), and Ventricular premature contractions (VPC--unifocal 40%; p < 0.05) as compared with control ECGs. Medium dose induced significant S. arrhythmia (62%; p < 0.001), A. ectopics (25%; p < 0.01), A. tachycardia (25%; p < 0.01), WPM (25%; p < 0.01), VPCs--unifocal (50%; p < 0.002), multifocal (25%; p < 0.01), couplets (25%; p < 0.01) and interpolated (25%; p < 0.01). High dose of caffeine revealed significant S. arrhythmia (56%; p < 0.002), A. ectopics (44%; p < 0.005), A. tachycardia (32%; p < 0.01), WPM (32%; p < 0.01) and VPCs--unifocal (64%; p < 0.001), multifocal (32%, p < 0.01), couplets (32%, p < 0.01), interpolated (32%; p < 0.01) and Ventricular tachycardia (VT) (20%; p < 0.01). A. flutter and fibrillation each were observed in two experiments only. In conclusion, these data indicate a dose dependent arrhythmogenecity of caffeine. Small dose, mostly, generated, benign arrhythmias due to vagal stimulation. More severe arrhythmias like VT, multifocal VPC. A. flutter and A. fibrillation were generated with higher dose of caffeine. Mechanism remains uncertain as caffeine has multiple actions. Further studies in human beings with normal and compromised myocardium may elucidate arrhythmogenic effects of caffeine.

Animals

Improvement in lung function measurements using a flow spirometer that emphasizes computer assessment of test quality.

We compared retrospective measurements of lung function from 101 steel workers using a commercially available spirometer to prospective lung function measurements performed, on average, 1.3 years later, with a newly developed spirometer. This spirometer was designed and developed to incorporate technology that provides immediate feedback on the quantitative and qualitative aspects of each forced expiratory effort. Of the 101 workers, 82 who had spirometry performed with each spirometer had at least two acceptable curves, and 51 workers tested with each spirometer had curves that met all American Thoracic Society (ATS) criteria for spirometry. No group showed the anticipated decline in forced expiratory volume in 1 second (FEV1) over time. The results showed an increased number of curves meeting ATS acceptability and reproducibility criteria, and a statistically significant increase in the FVC in all groups, and an increase in the FEV1 in the group encompassing all workers. Use of technology that strengthens the interaction between the spirometry technician, the data available to the technician on the computer, and the participant appears to represent true underlying lung function more accurately. Such an approach to the collection of lung function data should be considered by those evaluating spirometers for implementation in the workplace or pulmonary function laboratory as well as by those planning future spirometer development.

Humans

Exposure of rats to hyperoxia: alteration of lavagate parameters and macrophage function.

Exposure of rats to hyperoxia (100% oxygen for 64 h) resulted in striking alterations in the properties of samples obtained by bronchoalveolar lavage. The yield of neutrophils, lymphocytes, and red blood cells was increased, while the number of harvested alveolar macrophages decreased. The acellular lavage fluid level of protein was elevated, indicating lung damage. However, acellular phospholipid levels were unchanged. The ability of alveolar macrophages to produce reactive forms of oxygen in response to zymosan was significantly decreased by oxygen exposure. This impaired function was not fully explained by a decrease in viability of these phagocytes. In contrast, stimulant-induced chemiluminescence was elevated after hyperoxia. This rise was not due to a change in cellular antioxidant levels or to a discernible increase in arachidonic acid metabolites. However, it was associated with increased cellular lipid peroxidation.

Animals

Electron spin resonance investigation of laser and heated metal-tip-induced free radical formation in various tissues.

The short-lived free radical formation accompanying laser irradiation and laser-heated metal tip contact was examined using electron spin resonance (ESR) spin-trap methodology. Various tissues (canine myocardium, human aorta, liver, and spleen) were irradiated by argon-ion (continuous wave [CW] and pulse) and YAG (CW) lasers employing both naked fiber and a laser-heated metal tip. All showed the formation of primarily carbon-centered, not oxygenated, free radicals, together with some minor unidentified species. This implies that the backbones of amino acids, lipids, or other biological building blocks are cleaved during the irradiation or thermal treatment. Different tissues produce similar radicals but with different amounts when irradiated by argon-ion, YAG, and laser-heated metal tip sources. The amount of the free radicals formed depends on the laser power (within 5-15 W). Compared to the naked fiber, the laser-heated metal tip shows the generation of at least twice the amount of free radicals. The possible relationship of the free radical formation to tissue injury is briefly discussed.

Animals

Gastric emptying. A comparison of the Heineke-Mikulicz and Finney pyloroplasties with the Ramstedt pyloromyotomy.

Roentgenographic complete gastric emptying times using dilute barium were measured in 31 conditioned mongrel dogs (1) under normal or basal conditions, (2) after subdiaphragmatic complete truncal vagotomy, and (3) after four different methods of gastric drainage. The drainage procedures in 24 dogs were divided into four groups of six dogs each: (1) Heineke-Mikulicz two-layer (HM1) pyloroplasty; (3) Finney pyloroplasty (FP); and (4) the Ramstedt pyloromyotomy (RP). Using the same protocol for measuring complete gastric emptying, a fifth group of seven dogs underwent two gastric drainage procedures each: RP followed by subsequent conversion to the HM1. The statistical comparison to these procedures for adequacy of gastric drainage demonstrated no significant differences or superiority of any procedure in the groups of animals tested.

Animals